NCSTN [The Human Chemical-Genetic Interaction Map Project]

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======= NCSTN =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: NCSTN
  * **<color #00a2e8>Official Name</color>**: nicastrin
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=23385|23385]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q92542|Q92542]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=NCSTN&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20NCSTN|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/605254|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a type I transmembrane glycoprotein that is an integral component of the multimeric gamma-secretase complex. The encoded protein cleaves integral membrane proteins, including Notch receptors and beta-amyloid precursor protein, and may be a stabilizing cofactor required for gamma-secretase complex assembly. The cleavage of beta-amyloid precursor protein yields amyloid beta peptide, the main component of the neuritic plaque and the hallmark lesion in the brains of patients with Alzheimer's disease; however, the nature of the encoded protein's role in Alzheimer's disease is not known for certain. Mutations in this gene are associated with familial acne inversa. A pseudogene of this gene is present on chromosome 21. Alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Feb 2014]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:10993067, PubMed:12679784, PubMed:25043039, PubMed:26280335). The gamma- secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels. {ECO:0000269|PubMed:10993067, ECO:0000269|PubMed:12679784, ECO:0000269|PubMed:25043039, ECO:0000269|PubMed:26280335}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Nicastrin|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|amyloid precursor protein biosynthetic process|
|short-term synaptic potentiation|
|positive regulation of amyloid precursor protein biosynthetic process|
|gamma-secretase complex|
|amyloid-beta formation|
|Notch receptor processing, ligand-dependent|
|amyloid precursor protein catabolic process|
|Notch receptor processing|
|regulation of amyloid precursor protein biosynthetic process|
|amyloid precursor protein metabolic process|
|membrane protein intracellular domain proteolysis|
|central nervous system myelination|
|amyloid-beta metabolic process|
|positive regulation of glycoprotein biosynthetic process|
|axon ensheathment in central nervous system|
|positive regulation of glycoprotein metabolic process|
|membrane protein ectodomain proteolysis|
|dopamine receptor signaling pathway|
|membrane protein proteolysis|
|T cell proliferation|
|regulation of glycoprotein biosynthetic process|
|oligodendrocyte development|
|regulation of long-term synaptic potentiation|
|neuron apoptotic process|
|regulation of glycoprotein metabolic process|
|glutamate receptor signaling pathway|
|neuron death|
|integral component of presynaptic membrane|
|azurophil granule membrane|
|oligodendrocyte differentiation|
|endopeptidase activity|
|cellular response to calcium ion|
|lymphocyte proliferation|
|mononuclear cell proliferation|
|cellular response to dopamine|
|response to dopamine|
|ephrin receptor signaling pathway|
|epithelial cell proliferation|
|signal transduction involved in cellular response to ammonium ion|
|leukocyte proliferation|
|sarcolemma|
|melanosome|
|cellular response to catecholamine stimulus|
|cellular response to monoamine stimulus|
|cerebellum development|
|response to catecholamine|
|response to monoamine|
|myelination|
|myeloid cell homeostasis|
|glial cell development|
|ensheathment of neurons|
|axon ensheathment|
|metencephalon development|
|synaptic vesicle|
|Notch signaling pathway|
|cellular response to ammonium ion|
|adult behavior|
|hindbrain development|
|response to calcium ion|
|protein processing|
|glial cell differentiation|
|response to ammonium ion|
|regulation of synaptic plasticity|
|cellular response to metal ion|
|homeostasis of number of cells|
|endosome membrane|
|gliogenesis|
|cellular response to inorganic substance|
|protein maturation|
|T cell activation|
|early endosome|
|learning or memory|
|cognition|
|lysosomal membrane|
|response to metal ion|
|lymphocyte activation|
|cellular response to drug|
|focal adhesion|
|modulation of chemical synaptic transmission|
|regulation of trans-synaptic signaling|
|neutrophil degranulation|
|neutrophil activation involved in immune response|
|neutrophil mediated immunity|
|neutrophil activation|
|granulocyte activation|
|leukocyte degranulation|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|myeloid leukocyte mediated immunity|
|myeloid cell activation involved in immune response|
|peptide metabolic process|
|response to inorganic substance|
|cellular response to organic cyclic compound|
|cell population proliferation|
|behavior|
|myeloid leukocyte activation|
|cellular response to organonitrogen compound|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|positive regulation of apoptotic process|
|positive regulation of programmed cell death|
|cellular response to nitrogen compound|
|positive regulation of cell death|
|regulated exocytosis|
|enzyme linked receptor protein signaling pathway|
|brain development|
|leukocyte mediated immunity|
|head development|
|cellular amide metabolic process|
|exocytosis|
|response to organic cyclic compound|
|apoptotic process|
|leukocyte activation|
|central nervous system development|
|Golgi apparatus|
|response to organonitrogen compound|
|secretion by cell|
|endoplasmic reticulum|
|response to drug|
|export from cell|
|programmed cell death|
|cellular response to oxygen-containing compound|
|cell activation|
|response to nitrogen compound|
|immune effector process|
|cell death|
|secretion|
|cellular response to endogenous stimulus|
|mitochondrion|
|proteolysis|
|nervous system process|
|integral component of plasma membrane|
|organonitrogen compound biosynthetic process|
|positive regulation of catalytic activity|
|response to endogenous stimulus|
|regulation of apoptotic process|
|response to oxygen-containing compound|
|regulation of programmed cell death|
|neurogenesis|
|homeostatic process|
|cell development|
|regulation of cell death|
|positive regulation of protein metabolic process|
|macromolecule biosynthetic process|
|positive regulation of molecular function|
|immune response|
|positive regulation of macromolecule biosynthetic process|
|vesicle-mediated transport|
|system process|
|positive regulation of cellular biosynthetic process|
|membrane|
|gene expression|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp84|UM0125461 0.74μM R02 exp84]]|-2.32|
|[[:results:exp416|Tubacin 1.6μM R07 exp416]]|-1.89|
|[[:results:exp434|Vemurafenib 6.6μM R08 exp434]]|-1.83|
|[[:results:exp4|Actinomycin-D 0.01μM R00 exp4]]|-1.73|
|[[:results:exp459|Bleomycin 5μM R08 exp459]]|-1.73|
|[[:results:exp21|MLN-4924 0.2μM R00 exp21]]|-1.73|
|[[:results:exp507|Monensin 0.3μM R08 exp507]]|-1.72|
|[[:results:exp484|GSK-J5 1.5μM R08 exp484]]|1.7|
|[[:results:exp501|Methotrexate 0.01μM R08 exp501]]|1.95|
|[[:results:exp270|Campthothecin 0.001μM R06 exp270]]|1.96|
|[[:results:exp512|Olaparib 4μM R08 exp512]]|2.03|
|[[:results:exp294|Nutlin-3A 1.6μM R06 exp294]]|2.17|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 9109
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.57 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='NCSTN Expression in NALM6 Cells: 6.57'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>